A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86500
Title:
A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.
Authors:
Horwich, A; Oliver, R T; Wilkinson, Peter M; Mead, Graham M; Harland, S J; Cullen, M H; Roberts, J Trevor; Fossa, S D; Dearnaley, David P; Lallemand, E; Stenning, S P
Abstract:
The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.
Affiliation:
Radiotherapy Unit, Royal Marsden Hospital, Downs Rd, Sutton, Surrey, UK.
Citation:
A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party. 2000, 83 (12):1623-9 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Dec-2000
URI:
http://hdl.handle.net/10541/86500
DOI:
10.1054/bjoc.2000.1498
PubMed ID:
11104556
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHorwich, Aen
dc.contributor.authorOliver, R Ten
dc.contributor.authorWilkinson, Peter Men
dc.contributor.authorMead, Graham Men
dc.contributor.authorHarland, S Jen
dc.contributor.authorCullen, M Hen
dc.contributor.authorRoberts, J Trevoren
dc.contributor.authorFossa, S Den
dc.contributor.authorDearnaley, David Pen
dc.contributor.authorLallemand, Een
dc.contributor.authorStenning, S Pen
dc.date.accessioned2009-11-19T15:26:53Z-
dc.date.available2009-11-19T15:26:53Z-
dc.date.issued2000-12-
dc.identifier.citationA medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party. 2000, 83 (12):1623-9 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid11104556-
dc.identifier.doi10.1054/bjoc.2000.1498-
dc.identifier.urihttp://hdl.handle.net/10541/86500-
dc.description.abstractThe UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.en
dc.language.isoenen
dc.subjectCancer Metastasisen
dc.subjectCancer Stagingen
dc.subjectTesticular Canceren
dc.subject.meshAntineoplastic Agents-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarboplatin-
dc.subject.meshCisplatin-
dc.subject.meshEtoposide-
dc.subject.meshFollow-Up Studies-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshNeoplasm Staging-
dc.subject.meshNeutropenia-
dc.subject.meshSeminoma-
dc.subject.meshSurvival Analysis-
dc.subject.meshTesticular Neoplasms-
dc.subject.meshThrombocytopenia-
dc.subject.meshTime Factors-
dc.subject.meshTreatment Outcome-
dc.titleA medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.en
dc.typeArticleen
dc.contributor.departmentRadiotherapy Unit, Royal Marsden Hospital, Downs Rd, Sutton, Surrey, UK.en
dc.identifier.journalBritish Journal of Canceren

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